To investigate the role of gonadal steroids in the hypothalamic-pituitary-adrenal (HPA) response to stress, we studied adrenocorticotrophin (ACTH) and corticosterone (B) responses to 20-min restraint stress in cycling female rats, and in ovariectomized (OVX) rats replaced with physiological levels of estradiol (E2) and progesterone (P). In cycling rats, we found significantly higher peak ACTH (P less than 0.01) and B (P less than 0.05) responses to stress during proestrus compared to the estrous and diestrous phases. No differences were found in either basal ACTH and B levels across the cycle phases. In a separate study, OVX rats were maintained on low, physiological levels of E2 and P with silastic implants for 3 days, and injected either with oil (O'), 10 micrograms of E2 (E') 24 h before stress testing, or with E2 and 500 micrograms P 24 and 4 h, respectively, prior to stress (EP'). These treatments mimicked endogenous profiles of E2 and P occurring during diestrous, proestrous, and late proestrous-early estrous phases, respectively. In response to stress, ACTH levels were higher (P less than 0.01) in the E' group compared to the EP' and O' groups. Although the peak B response was similar in all groups, the E' and EP' groups secreted more B after the termination of stress than did the O' group. Within the 20 min stress period, ACTH levels in the E' group were significantly (P less than 0.05) higher at 5, 10, and 15 min after the onset of stress, compared to the EP' and O' groups. Plasma B levels were significantly higher in the E' group at 5 and 10 min (P less than 0.05 and P less than 0.01, respectively) compared to the EP' and O' group. beta-endorphin-like immunoreactive responses to restraint stress were also significantly higher in the E' group compared to the EP' (P less than 0.05) and O' (P less than 0.01) groups. In contrast to the effect seen at 24 h, ACTH responses to stress 48 h after E2 injection in the E' group were comparable to O' animals. There was no effect of E2 on ACTH clearance, whereas B clearance was enhanced in E' treated animals vs. O'-treated animals. These results indicate that the HPA axis in the female rat is most sensitive to stress during proestrous. Such enhanced HPA responses to stress are limited to the early portion of proestrous, as progesterone appears to inhibit the facilitatory effects of estrogen on ACTH release during stress. Taken together, these results suggest an ovarian influence on both activational and inhibitory components of HPA activity.

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Variations in the Hypothalamic-Pituitary-Adrenal Response to Stress during the Estrous Cycle in the Rat

The steroidogenic pathway within the ovary gives rise to progestins, androgens and oestrogens, all of which act via specific nuclear receptors to regulate reproductive function and maintain fertility. The role of progestins in follicular growth and development is limited, its action confined largely to ovulation, although direct effects on granulosa cell function have been reported. Consistent with these findings, progesterone receptor knockout mice are infertile because they cannot ovulate. Androgens have been shown to promote early follicular growth, but also to impede follicular development by stimulating atresia and apoptosis. The inability of androgens to transduce a signal in mice lacking androgen receptors culminates in reduced fertility. Oestrogens are known to exert effects on granulosa cell growth and differentiation in association with gonadotrophins. Studies with oestrogen receptor knockouts and oestrogen depleted mice have shown us that oestrogen is essential for folliculogenesis beyond the antral stage and is necessary to maintain the female phenotype of ovarian somatic cells. In summary, the action of steroids within the ovary is based on the developmental status of the follicle. In the absence of any single sex steroid, ovarian function and subsequently fertility, are compromised.

/pdf/the-role-of-steroids-in-follicular-growth-4pa9phdbp3.pdf

The role of steroids in follicular growth.

Puberty and structural brain development in humans.

A prospective, controlled study of the effects of hormonal contraception on bone mineral density ☆

The endometrium undergoes cyclic growth and development with the sole purpose of successful establishment of pregnancy. As more is known about the gene products of the endometrium, it appears that many of the secreted products of the glandular epithelium function to support the nascent embryo and begin the early communication that continues into pregnancy. Maternal endometrial cells are regulated directly by ovarian steroids and indirectly by various growth factors and cytokines. The time of maximal uterine receptivity is now thought to arise on cycle days 20-24 and is manifest by the expression of many different endometrial products. These proteins can serve as markers of uterine receptivity and have been used to identify women at risk for implantation failure. The use of marker proteins promises to promote our understanding of the mechanism of implantation while providing clues into the causes of some types of infertility. Ultimately, the endometrium provides the opportunity for the embryo while at the same time maintaining constraints on uncontrolled invasion of the 'tumour-like' placenta. Understanding this subject in greater detail will likely improve health care opportunities for the infertile couple and provide new insights into contraception targeting the endometrium and embryo-endometrial interactions.

/pdf/endothelial-cell-dysfunction-following-prolonged-activation-2l44peqbqp.pdf

Endothelial cell dysfunction following prolonged activation of progesterone receptor

Clinical effects of orally administered extracts of Montanoa tomentosa in early human pregnancy.

Return of ovulation following a single injection of depo-medroxyprogesterone acetate: a pharmacokinetic and pharmacodynamic study.

Studies on ovarian and adrenal steroids at different phases of the menstrual cycle

Studies on ovarian and adrenal steroids at different phases of the menstrual cycle: II. A comparative assessment of the circadian variation in steroid and lutropin levels during the follicular, periovulatory and luteal phases

A.-R. Aedo

Papers

Clinical effects of orally administered extracts of Montanoa tomentosa in early human pregnancy.

Return of ovulation following a single injection of depo-medroxyprogesterone acetate: a pharmacokinetic and pharmacodynamic study.

Studies on ovarian and adrenal steroids at different phases of the menstrual cycle

Studies on ovarian and adrenal steroids at different phases of the menstrual cycle: II. A comparative assessment of the circadian variation in steroid and lutropin levels during the follicular, periovulatory and luteal phases

Studies on ovarian and adrenal steroids at different phases of the menstrual cycle: 1. Dynamic changes during the periovulatory period